Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats
Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats
复制标题
DOI：
10.1523/jneurosci.13-03-01035.1993
复制
发表时间：
1993-03
期刊：
影响因子：
--
通讯作者：
C. Blaha;P. Winn
中科院分区：
文献类型：
--
作者：
C. Blaha;P. Winn
采用活体计时电流法和脑内微透析技术，观察了黑质致密部微量注射胆碱能药物对乌拉坦麻醉大鼠背内侧前纹状体多巴胺(DA)外流的影响。黑质微量注射胆碱能激动剂尼古丁或卡巴胆碱后，纹状体DA外流呈剂量依赖性增加，表现为计时电流信号的增加。通过黑质内注射胆碱酯酶抑制剂新斯的明来增加黑质细胞外ACh的浓度，也会导致纹状体DA溢出所对应的计时电流信号的增加。在体微透析法证实了新斯的明对纹状体DA外流的刺激作用。与假手术对照组动物相比，损毁桥脑脚盖核(PPTg)喹啉酸可减弱黑质内新斯的明对纹状体DA外流的刺激作用。相反，黑质注射直接的ACh受体激动剂尼古丁后，这些治疗导致纹状体DA流出增加。这些结果提示，PPTG胆碱能神经元通过调节大鼠黑质DA神经元的活动，间接参与了纹状体活动的调节。
The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.